Positive inotropic effects of Tityus cambridgei and T. serrulatus scorpion venoms on skeletal muscle.
Toxins that block voltage-dependent K+ channels and those that modify Na+ channel gating exhibit positive inotropic effect on skeletal muscle. We compared the effect of the venom of Tityus cambridgei (Tc) and Tityus serrulatus (Ts) scorpions on mouse diaphragm force, in vitro. In indirect and direct (using D-tubocurarine 7.3 microM) stimulation, Tc, 10microg/mL, increased the contractile force, an effect prevented by tetrodotoxin (TTX) while Ts, 0.5 microg/mL, potentiated only indirectly stimulated diaphragm, thus indicating its activity is mainly mediated through acetylcholine release from nerve terminal. This effect is prevented by TTX and attenuated by the K+ channel opener cromakalim. In conclusion, our data show that while the positive inotropic effect of both venoms appears associated to the activity of Na+ and K+ channels, only Tc venom acts also directly on skeletal muscle. This finding call for further studies on Tc venom to identify the toxin responsible for its direct inotropic activity as it may have clinical applications.
Borja-Oliveira
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CR
Centro de Biologia Molecular e Estrutural (CEBIME), Laboratorio Nacional de Luz Sincrotron-LNLS, Caixa Postal 6192, 13084-971, Campinas SP, Brazil.
Pertinhez
T A
TA
Rodrigues-Simioni
L
L
Spisni
A
A
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D053580:Muscle Strength / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology
D003473:Neuromuscular Nondepolarizing Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019806:Cromakalim; D013779:Tetrodotoxin; D000109:Acetylcholine; D014403:Tubocurarine